Pharmacologic nephrectomy with chronic angiotensin converting enzyme inhibitor treatment in renovascular hypertension in the rat.
Angiotensin converting enzyme (ACE) inhibitor treatment in renovascular hypertension is associated with acute compromise of renal function in patients with bilateral renal artery stenosis or with arterial stenosis to a single functioning kidney. Recent evidence has suggested that renal function is also compromised in the stenosed kidney of patients with unilateral renal artery stenosis. The long-term consequence of this reduction in renal function is not known. We have studied the effect of chronic ACE inhibition with enalapril on renal structure and function in rats with the two-kidney one-clip model of renovascular hypertension. Four weeks after placement of a clip on the left renal artery, hypertensive rats were randomized to treatment with enalapril, minoxidil, or to a no treatment group. Twelve months later split kidney function was determined by chromium 51-labeled ethylenediamine-tetraacetic acid clearance in surviving rats. Clearance of the clipped kidney was 0.0 ml/min (enalapril group), 0.26 +/- 0.23 ml/min (minoxidil group), and 0.74 +/- 0.13 ml/min (untreated group). The clipped kidney from the enalapril treated rats weighed much less than the minoxidil group or the untreated group (0.46 +/- 0.1 gm, 1.2 +/- 0.07 gm, and 1.14 +/- 0.10 gm, respectively). Enalapril treatment was stopped for 2 weeks in five rats. The clipped kidney remained small and nonfunctional. Histologic examination revealed marked interstitial fibrosis and tubular atrophy of the clipped kidneys from the enalapril treated group in contrast to minor changes in the minoxidil treated and untreated groups. After 12 months of treatment, survival in the enalapril group was 84%, 48% in the minoxidil group, and 15% in the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)
Jackson
B
B
Department of Medicine, University of Melbourne, Austin Hospital, Victoria, Australia.
Franze
L
L
Sumithran
E
E
Johnston
C I
CI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D006978:Hypertension, Renovascular / Q000188:drug therapy*; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D008914:Minoxidil / Q000494:pharmacology / Q000627:therapeutic use; D009392:Nephrectomy; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D008914:Minoxidil; D004656:Enalapril